Otitis media with effusion (OME) is one of the largest public health problems of young children. The inflammatory events that occur in OME lead to effusion and tissue hyperplasia that in turn can produce temporary and permanent hearing loss. Immune responses play a critical role in OME. Immunity is intimately involved in the host response to infection in the middle ear (ME), and provides the primary defense of the ME from infection. In addition, immune-mediated inflammation has been implicated in OME pathogenesis. In the current application, we propose to study the cellular and molecular mechanisms that control immunity and tissue proliferation in the ME. We will identify the endothelial cell receptors that control the recruitment of leukocytes into the ME cavity during OME, and determine whether these receptors can be inhibited. We will investigate cytokines that regulate the expression of systemic and local mucosal immunity in the ME, and explore procedures to increase the ME immune response to bacterial antigens. We will also identify the growth factors and receptors that are present in the ME mucosa during hyperplasia, and document their ability to stimulate cell proliferation in the mucosa both in vitro and in vivo. Finally, we will test inhibitors of growth factor receptors to determine whether mucosal hyperplasia can be ameliorated or reversed during OME.